Metformin promotes smear conversion in tuberculosis‐diabetes comorbidity and construction of prediction models

Abstract

Background The comorbidity of tuberculosis (TB) and diabetes mellitus (DM) is a global health concern. Metformin is commonly used in DM but the potential effectiveness in comorbid patients is uncertain. This retrospective study aims to investigate the effect of metformin on TB‐DM comorbidity and construct prediction models. Methods Patients diagnosed with TB‐DM in West China Hospital were retrospectively enrolled from Nov 2013 to Sep 2019. Electronic health records of patients were extracted. Two‐month smear conversion (2SC) was considered an outcome indicator of TB. Univariate and multivariate logistic regression (LR) were used to assess the role of metformin and other independent predictors. Meanwhile, prediction models were built by LR, elastic net regression, support vector machine, k‐nearest neighbors, and random forest. Results A total of 927 individuals were recruited, among which 408 (44.01%) were metformin‐exposed patients. A higher 2SC rate was observed in the metformin users. Other impact factors such as smoking, glucose, and creatinine levels were also identified. Multivariable models were then constructed using filtered variables. The support vector machine model yields the highest AUC (0.808, 95% CI: 0.767–0.849) and specificity (83.24%). LR model outperformed others in terms of sensitivity (69.71%). Conclusion This retrospective study of a large population from southwestern China provides strong clinical evidence for the positive effects of metformin in TB‐DM. Metformin is associated with a better therapeutic outcome and promising for the adjuvant therapy of TB‐DM. Furthermore, a combination of support vector machine and LR models is recommended to discriminate the patients with poor treatment outcomes.

Impact of diabetes mellitus on tuberculosis treatment outcomes: a cohort study in Bengaluru, India

“…These issues are paralleled in global studies, including Wang et al, who explore the potential role of metformin in improving TB treatment outcomes in TB-DM comorbidity, Wang et al, and Karoli et al, who examine the significance of vitamin D deficiency in managing TB-DM comorbidity. 16,17 Our findings of poorer outcomes and increased ADRs in TB-DM patients reflect the dual burden of these diseases, as underscored by Aweis et al and Babu et al 18,19 The study underscores the urgent need for integrated TB and DM management approaches, advocating for tailored treatment regimens, comprehensive patient education, and the utilization of advanced technologies like artificial intelligence. The study also highlights the importance of strengthening follow-up strategies and enhancing healthcare provider training to improve patient care and the outcomes for those affected by the TB-DM comorbidity.…”

The advances in adjuvant therapy for tuberculosis with immunoregulatory compounds

“…Metformin could increase host cells production of mitochondrial ROS and the acidification of mycobacterium phagosome, promote the proliferation of T cells secreting IFN-γ, reduce the bacterial load, TB-induced tissue pathology and inflammatory response in both lung and spleen of mice, and enhance the host-specific immune function ( Singhal et al, 2014 ). Secondly, metformin treatment reduced soluble CD14, CD163, and inflammatory C-reactive protein levels in TB patients with diabetes, significantly decreased MMP-1, −2, −3, −7, −9, and − 12 levels, and promoted smear conversion, indicating that metformin has significant anti-inflammatory and lung injury improvement effects, and greatly reduced mortality ( Degner et al, 2018 ; Kumar et al, 2018 ; Kumar N. P. et al, 2019 ; Li et al, 2021 ; Wang Y. et al, 2022 ). In addition, metformin also could induce autophagy, regulate oxidative stress, and enhance the efficacy of anti-TB drugs ( Fatima et al, 2021 ).…”

“…However, SASP could enhance the Mtb clearance activity of macrophages by activating NADPH oxidase to promote the oxidation of mycothiol in Mtb macrophages, rather than the metabolite-producing 5-aminosalicylic acid ( Cai et al, 2016 ). Previous studies have shown that SASP could significantly reduce the Mtb bactericidal load and histopathological inflammation of lungs in mice, and prevent severe inflammation induced by Mtb infection of human macrophages ( Cai et al, 2016 ; Wang Y. et al, 2022 ).…”